tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Much more needed in natural history of Alagille syndrome
Authors: Satender Pal Singh, Nitisha Mondia
Journal: Hepatology (2023)

To the editor, We read with great interest the study by Vandriel et al., "Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The GALA Study." In this multicentre retrospective study only 40.3% of children reach adulthood with their native liver. The study also shows bilirubin <5.0 mg/dL between 6 and 12 months of age is associated with better hepatic outcomes.1 Furthermore, this study has the largest cohort of Alagille syndrome patients and will assist in understanding and managing patients. However certain points needs more insight. Firstly, Alagille syndrome patients have right sided heart disease and which determines the patient survival either without transplant or with transplant. The study mentions that cardiac disease is present in 91% (n=1231/1347), but should have also elucidated more on the type of cardiac abnormality seen in these patients. More severe cardiac deformity makes them unable to undergo dobutamine stress testing, which is mandatory according to King's College guidelines for these Alagille patients.2 Secondly, the study showed renal involvement seen in 39% (n=500/1275). The study should have also illustrated the type of kidney injury, how many had renal tubular acidosis (seen with Alagille syndrome), what was the level of renal injury (stages of acute kidney injury) and whether it was reversible with therapy or not. As 4 patients underwent combined liver-kidney transplant, knowing type of acute kidney injury in these patients might help in managing them in future.3 Thirdly, the showed that 345 patients underwent isolated liver transplant. The study should mention immunosuppression details in these patients as they are known to preserve renal function. The literature mentions early introduction of mechanistic target of rapamycin (mTOR) inhibitors.4 Lastly, the study does not mention the growth and development of the Alagille patients as previous literature shows growth problems do not improve in these patients even after successful liver transplantation.5 CONFLICT OF INTEREST The authors have no conflicts to report.
Association Between State-Level Medicaid Expansion and Eviction Rates
Authors: Sebastian Linde, Leonard E. Egede
Journal: JAMA Network Open (2023)

Importance Prior research has identified associations between housing insecurity and poor health outcomes. Objective To evaluate the association between US state Medicaid expansions and reductions in eviction; to examine the persistence of these associations and how they vary across US states and counties. Design, Setting, and Participants This cohort study of 25 398 county-year observations (across 40 states) used US eviction and census data for the years 2002 through 2018 (ie, 17 years). County-level associations were estimated using interactive fixed effects counterfactual estimators, and models were selected using cross validation. Across-county treatment association heterogeneities were assessed using multivariable regression methods. Analyses were performed in July of 2022. Exposure State-level Medicaid expansion under the Patient Protection and Affordable Care Act. Main Outcomes and Measures Eviction judgments; eviction judgments per 100 renter-occupied households. Results Among a total of 774 treated counties (with Medicaid expansion) and 720 control counties (untreated, without Medicaid expansion), mean (SD) eviction judgments for treated counties were 534.78 (1945.84) eviction judgments in the pre-2014 period (mean [SD] eviction rate, 2.25 [2.18] per 100 households), which decreased to 463.67 (1499.39) eviction judgments in the post-2014 period (mean [SD] eviction judgment rate, 2.02 [1.81] per 100 households). Control group mean (SD) county eviction judgments were 477.22 (1592.18) eviction judgments (mean [SD] eviction judgment rate, 1.91 per 100 households) pre-2014, and 490.22 (1575.19) eviction judgments (mean [SD] eviction judgment rate, 1.89 per 100 households) post-2014. Model estimates indicate that Medicaid expansion was associated with reductions in county eviction judgments by −66.49 (95% CI, −132.50 to −0.48; P = .047) and reductions of the eviction judgment rate by −0.25 (95% CI, −0.35 to −0.14; P &amp;amp;lt; .001). Associations remained broadly consistent between 2014 and 2018, although some diminishment of associations occurred in 2018. Approximately 29% of the across-county treatment association variation was explained by across-state differences, while 9% was explained by county-level demographic and uninsurance differences. Conclusions and Relevance In this cohort study, Medicaid expansion was associated with reductions in eviction judgments and eviction judgment rates; however, these associations were found to vary considerably both across as well as within states (across counties). These findings suggest that the channel between Medicaid expansion and evictions is sensitive to state environments as well as county specific population demographics and uninsurance levels.
Erratum: “A Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods”
Authors: Drew B. Day, Sheela Sathyanarayana, Kaja Z. LeWinn, Catherine J. Karr, W. Alex Mason, Adam A. Szpiro
Journal: Environmental Health Perspectives (2023)

Vol. 131, No. 1 ErratumOpen AccessErratum: “A Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods”is correction ofA Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods Drew B. Day, Sheela Sathyanarayana, Kaja Z. LeWinn, Catherine J. Karr, W. Alex Mason, and Adam A. Szpiro Drew B. Day https://orcid.org/0000-0003-2606-2050 Search for more papers by this author , Sheela Sathyanarayana Search for more papers by this author , Kaja Z. LeWinn Search for more papers by this author , Catherine J. Karr Search for more papers by this author , W. Alex Mason Search for more papers by this author , and Adam A. Szpiro Search for more papers by this author Published:11 January 2023CID: 019001https://doi.org/10.1289/EHP12564AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit In the Discussion, in the third paragraph of the “Comparing Simulation Results to Prior Evaluations of Mixture Exposure Model Performance” section, the authors stated, “Furthermore, the mixture component-specific coefficients estimated by quantile g-computation were far more biased than those of any of the WQSr models.” Given that the mean absolute percent error (MAPE) that the authors used in their analyses assesses accuracy rather than bias, the correct statement should be as follows: “Furthermore, the mixture component-specific coefficients estimated by quantile g-computation were far less accurate than those of any of the WQSr models.”The authors regret the error.FiguresReferencesRelatedDetailsRelated articlesA Permutation Test-Based Approach to Strengthening Inference on the Effects of Environmental Mixtures: Comparison between Single-Index Analytic Methods30 August 2022Environmental Health Perspectives Vol. 131, No. 1 January 2023Metrics About Article Metrics Publication History Manuscript received8 December 2022Manuscript accepted15 December 2022Originally published11 January 2023 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.
Letter to the Editor: Learning more about the safety of atezolizumab plus bevacizumab in patients with hepatocellular carcinoma
Authors: Chia-Chi Wang, Jia-Horng Kao
Journal: Hepatology (2023)

To the editor, We read with great interest the article by D’Alessio A et al.1 In this multicenter retrospective study of 216 HCC patients receiving AtezoBev treatment with a median follow-up of 9 months, they found comparable rate of treatment-related adverse events (trAEs) between patients with Child-Pugh (CP)-A and those with CP-B. In addition, the presence and grades of varices on esophagogastroduodenoscopy (EGD) before treatment did not correlate with bleeding events, suggesting that HCC patients with CP-B had similar tolerability compared with those with CP-A in routine clinical practice. Although these results could provide real-world evidence about the safety of AtezoBev, especially in the treatment of HCC patients with CP-B, several issues are worthy of discussion. First, in this study, bleeding events occurred in 14% (28/200) of the population. Of 12 patients with grade 3 or 4 bleeding events, 9 (75%) were due to gastroesophageal varices bleeding. Although prophylactic band ligation for high-risk varices may reduce the risk of esophageal varices bleeding (EVB) in patients with cirrhosis, whether it remains effective in HCC patients receiving AtezoBev is largely unknown.2 The authors may explore this issue by adding a figure to display the number of EVB in relation to the grade of varices at pretreatment EGD. In addition, further analysis was suggested to compare the rate of EVB between patients with porphylactic band ligation (n=26) and those without. Second, patients should undergo EGD within 6 months before initiation of treatment and high-risk varices should be treated in the IMbrave 150 trial.3 In this real-world study, 94 patients (47%) did not undergo EGD before treatment. The authors may explore whether there was a higher rate of EVB in those without pretreatment EGD. Finally, liver reserve is known to correlate with overall survival and is an important factor of eligibility for sequential therapy after the failure of first-line systemic therapy in HCC patients. Albumin-bilirubin (ALBI) grade is a reproducible and objective measure of liver function reserve in HCC patients.4 The readers may have interest in learning the serial change of ALBI grade between CP-A and CP-B patients during AtezoBev treatment to understand more about their effect on the preservation of liver function. CONFLICT OF INTEREST The authors have no conflicts to report. AUTHORSHIP STATEMENT All authors approved the final version of the manuscript.
TWEAK/FN14 promotes profibrogenic pathway activation in Prominin-1-expressing hepatic progenitor cells in biliary atresia
Authors: Celia Short, Allen Zhong, Jiabo Xu, Elaa Mahdi, Alison Glazier, Nicolas Malkoff, Nicolas Noriega, Theresa Yeo, Kinji Asahina, Kasper S. Wang
Journal: Hepatology (2023)

Biliary atresia (BA), a congenital cholestatic liver disease, commonly culminates in end-stage liver disease. We previously demonstrated in BA that Prominin-1 ( Prom1 )-expressing hepatic progenitor cells (HPCs) expand within regions of developing fibrosis, giving rise to cholangiocytes within biliary ductular reactions. Null mutation of Prom1 or ablation of cells expressing Prom1 significantly diminishes fibrogenesis. FN14, the receptor for TNF-like weak inducer of apoptosis (TWEAK), is expressed by HPCs. TWEAK/FN14 signaling promotes fibrosis in multiple organ systems. Therefore, we hypothesized that TWEAK/FN14 signaling mediates Prom1 -expressing HPC proliferation leading to profibrogenic ductular reactions in BA.The experimental mouse model of BA mediated by perinatal rhesus rotavirus (RRV) infection resulted in increased co-expression of Fn14 in Prom1 -expressing HPCs within regions of ductular reactions. FN14 antagonist L524-0366 decreased ductular reactions, biliary fibrosis and periportal fibroblast activation in RRV injury. L524-0366 inhibition also demonstrated loss of downstream noncanonical NF-kB signaling expression in RRV injury. Murine HPC organoids demonstrated accelerated organoid growth and proliferation when treated with recombinant TWEAK. Increased organoid proliferation with recombinant TWEAK was lost when also treated with L524-0366. Analysis of a large publicly available RNA sequencing database of BA and normal control patients revealed significant increases in expression of PROM1 , FN14 , and genes downstream of TNF signaling and noncanonical NF-κB signaling pathways in BA infants. Infants who failed to achieve bile drainage after hepatoportoenterostomy had higher relative levels of FN14 expression.TWEAK/FN14 signaling activation in Prom1 -expressing HPCs contributes to proliferation of profibrogenic ductular reactions in BA.
Effect of High-Dose Selenium on Postoperative Organ Dysfunction and Mortality in Cardiac Surgery Patients
Authors: Christian Stoppe, Bernard McDonald, Patrick Meybohm, Kenneth B. Christopher, Stephen Fremes, Richard Whitlock, Siamak Mohammadi, Dimitri Kalavrouziotis, Gunnar Elke, Rolf Rossaint, Philipp Helmer, Kai Zacharowski, Ulf Günther, Matteo Parotto, Bernd Niemann, Andreas Böning, C. David Mazer, Philip M. Jones, Marion Ferner, Yoan Lamarche, Francois Lamontagne, Oliver J. Liakopoulos, Matthew Cameron, Matthias Müller, Alexander Zarbock, Maria Wittmann, Andreas Goetzenich, Erich Kilger, Lutz Schomburg, Andrew G. Day, Daren K. Heyland, Gregory Hare, Michael WA Chu, Pierre Voisine, Francois Dagenais, Eric Dumont, Frédérique Jacques, Eric Charbonneau, Jean Perron, Simone Lindau, Roupen Hatzakorizan, Assad Haneya, Georg Trummer, Angela Jareth, Xuran Jiang, Ellen Dresen, Aileen Hill
Journal: JAMA Surgery (2023)

Selenium contributes to antioxidative, anti-inflammatory, and immunomodulatory pathways, which may improve outcomes in patients at high risk of organ dysfunctions after cardiac surgery.To assess the ability of high-dose intravenous sodium selenite treatment to reduce postoperative organ dysfunction and mortality in cardiac surgery patients.This multicenter, randomized, double-blind, placebo-controlled trial took place at 23 sites in Germany and Canada from January 2015 to January 2021. Adult cardiac surgery patients with a European System for Cardiac Operative Risk Evaluation II score-predicted mortality of 5% or more or planned combined surgical procedures were randomized.Patients were randomly assigned (1:1) by a web-based system to receive either perioperative intravenous high-dose selenium supplementation of 2000 μg/L of sodium selenite prior to cardiopulmonary bypass, 2000 μg/L immediately postoperatively, and 1000 μg/L each day in intensive care for a maximum of 10 days or placebo.The primary end point was a composite of the numbers of days alive and free from organ dysfunction during the first 30 days following cardiac surgery.A total of 1416 adult cardiac surgery patients were analyzed (mean [SD] age, 68.2 [10.4] years; 1043 [74.8%] male). The median (IQR) predicted 30-day mortality by European System for Cardiac Operative Risk Evaluation II score was 8.7% (5.6%-14.9%), and most patients had combined coronary revascularization and valvular procedures. Selenium did not increase the number of persistent organ dysfunction-free and alive days over the first 30 postoperative days (median [IQR], 29 [28-30] vs 29 [28-30]; P = .45). The 30-day mortality rates were 4.2% in the selenium and 5.0% in the placebo group (odds ratio, 0.82; 95% CI, 0.50-1.36; P = .44). Safety outcomes did not differ between the groups.In high-risk cardiac surgery patients, perioperative administration of high-dose intravenous sodium selenite did not reduce morbidity or mortality. The present data do not support the routine perioperative use of selenium for patients undergoing cardiac surgery.ClinicalTrials.gov Identifier: NCT02002247.
Checkpoint inhibitor‐based salvage regimens prior to autologous stem cell transplant improve event‐free survival in relapsed/refractory classic Hodgkin lymphoma
Authors: Sanjal H. Desai, Michael A. Spinner, Kevin David, Veronika Bachanova, Gaurav Goyal, Brad Kahl, Kathleen Dorritie, Jacques Azzi, Vaishalee P. Kenkre, Sally Arai, Cheryl Chang, Brendon Fusco, Nuttavut Sumransub, Haris Hatic, Raya Saba, Uroosa Ibrahim, Elyse I. Harris, Harsh Shah, Jacob Murphy, Stephen Ansell, Deepa Jagadish, Victor Orellana‐noia, Catherine Diefenbach, Siddharth Iyenger, K. C. Rappazzo, Rahul Mishra, Yun Choi, Grzegorz S. Nowakowski, Ranjana H. Advani, Ivana N. Micallef
Journal: American Journal of Hematology (2023)

Abstract Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant‐eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)‐based regimens before ASCT. Study endpoints included event‐free survival (EFS), progression‐free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI‐based regimens prior to ASCT. When adjusted for time to relapse, pre‐ASCT response and use of BV maintenance, patients receiving CPI‐based regimens had superior 2‐year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p &lt; .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI‐based regimens were associated with superior 2‐year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03–0.5, p &lt; .0001). OS did not differ by pre‐ASCT salvage regimen. In this large multicenter retrospective study, CPI‐based regimens improved EFS and PFS compared to other salvage regimens independent of pre‐ASCT response. These data support earlier sequencing of CPI‐based regimens in R/R cHL in the pre‐ASCT setting.
Light-Related Cutaneous Symptoms of Erythropoietic Protoporphyria and Associations With Light Sensitivity Measurements
Authors: Haya S. Raef, Lina Rebeiz, Rebecca Karp Leaf, Olivia Hughes, Paul Jiang, Abrahim ElSeht, Karl E. Anderson, Kristen Wheeden, Irene Kochevar, Sarina B. Elmariah, Amy K. Dickey
Journal: JAMA Dermatology (2023)

Erythropoietic protoporphyria (EPP) is a rare and underdiagnosed genetic disease characterized by painful sensitivity to light. A better understanding and characterization of its light-induced cutaneous symptoms may aid in the identification of EPP in patients.
Metabolic reprogramming and its clinical implication for liver cancer
Authors: Flora Yang, Leena Hilakivi-Clarke, Aurpita Shaha, Yuanguo Wang, Xianghu Wang, Yibin Deng, Jinping Lai, Ningling Kang
Journal: Hepatology (2023)

Cancer cells often encounter hypoxic and hypo-nutrient conditions, which force them to make adaptive changes to meet their high demands for energy and various biomaterials for biomass synthesis. As a result, enhanced catabolism (breakdown of macromolecules for energy production) and anabolism (macromolecule synthesis from bio-precursors) are induced in cancer. This phenomenon is called “metabolic reprogramming,” a cancer hallmark contributing to cancer development, metastasis, and drug resistance. HCC and cholangiocarcinoma (CCA) are 2 different liver cancers with high intertumoral heterogeneity in terms of etiologies, mutational landscapes, transcriptomes, and histological representations. In agreement, metabolism in HCC or CCA is remarkably heterogeneous, although changes in the glycolytic pathways and an increase in the generation of lactate (the Warburg effect) have been frequently detected in those tumors. For example, HCC tumors with activated β-catenin are addicted to fatty acid catabolism, whereas HCC tumors derived from fatty liver avoid using fatty acids. In this review, we describe common metabolic alterations in HCC and CCA as well as metabolic features unique for their subsets. We discuss metabolism of NAFLD as well, because NAFLD will likely become a leading etiology of liver cancer in the coming years due to the obesity epidemic in the Western world. Furthermore, we outline the clinical implication of liver cancer metabolism and highlight the computation and systems biology approaches, such as genome-wide metabolic models, as a valuable tool allowing us to identify therapeutic targets and develop personalized treatments for liver cancer patients.
Living-Donor Liver Transplant for Patients With End-stage Liver Disease
Authors: Chengcheng Zhang, Yanjiao Ou, Leida Zhang
Journal: JAMA Surgery (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Glyphosate exposure and urinary oxidative stress biomarkers in the Agricultural Health Study
Authors: Vicky C Chang, Gabriella Andreotti, Maria Ospina, Christine G Parks, Danping Liu, Joseph J Shearer, Nathaniel Rothman, Debra T Silverman, Dale P Sandler, Antonia M Calafat, Laura E Beane Freeman, Jonathan N Hofmann
Journal: JNCI Journal of the National Cancer Institute (2023)

Glyphosate is the most widely applied herbicide worldwide, and its use has been associated with increased risks of certain hematopoietic cancers in epidemiologic studies. Animal and in vitro experiments suggest that glyphosate may induce oxidative stress, a key characteristic of carcinogens; however, evidence in human populations remains scarce. We investigated associations between glyphosate exposure and urinary oxidative stress biomarkers in the Biomarkers of Exposure and Effect in Agriculture study, a molecular epidemiologic subcohort in the Agricultural Health Study.
SULT2B1-CS-DOCK2 axis regulates effector T-cell exhaustion in HCC microenvironment
Authors: Shuai Wang, Rui Wang, Nan Xu, Xuyong Wei, Yijie Yang, Zhengxing Lian, Beini Cen, Chenchen Shen, Wangyao Li, Jianguo Wang, Zhensheng Zhang, Linsong Tang, Qiang Wei, Di Lu, Xiao Xu
Journal: Hepatology (2023)

HCC is a malignant disease. Compared with tyrosine kinase inhibitors (the classical therapy), immune checkpoint inhibitors are more effective in the treatment of HCC, despite their limited efficacy. Among these restricted factors, exhaustion of tumor-infiltrated lymphocytes, especially CD8 + T cells, is a core event. We aimed to determine the key factors contributing to CD8 + T-cell infiltration in HCC and investigate the underlying mechanisms.